Neonatal asphyxia is commonly encountered in early life and associated with a high risk of brain injury and major irreversible neurological problems in surviving children; including cerebral palsy, mental retardation, and epilepsy. Despite the magnitude of the clinical problem, there is little information on how asphyxia affects the cerebral circulation of newborns. The proposed research will explore the responses of neonatal cerebral circulation to asphyxia. Preliminary evidence, presented here, suggests that some of these responses may be neurogenically mediated. Thus, the role the sympathetic nervous system may play in the changes in cerebral circulation that occur during asphyxia will also be investigated. Determinations of cerebral blood flow (CBF) by a modification of the Kety and Schmidt technique employing 133 Xenon as indicator, and regional cerebral blood flow (rCBF) by autoradiographic method using 14C-iodoantipyrine, will be utilized to study the cerebral circulation during asphyxia. These studies will be conducted in newborn dogs, animals that parallel human newborns in terms of growth and neurological development. In the present studies, cerebral circulatory responses will be determined immediately after brief asphyxia, or after varying periods of survival. In addition, the same cerebral vascular responses will be studied after removal of the superior cervical ganglion, the origin of most of the major cerebral arteries' sympathetic innervation, or the pharmacological blockade of these nerves. The basic studies proposed here on the effects of asphyxia on the neonatal cerebral circulation constitute a necessary first step toward the long range goal of improving the management of these conditions.